biostudies-literatureChen XNHLBI NIH HHSAustralian Research Council689-700https://www.ebi.ac.uk/biostudies/studies/S-EPMC7925372biostudies-literatureUnknown19(3)<h4>Background</h4>Vitamin K antagonists (VKAs), such as warfarin, have remained the cornerstone of oral anticoagulation therapy in the prevention and treatment of thromboembolism for more than half a century. They function by impairing the biosynthesis of vitamin K-dependent (VKD) clotting factors through the inhibition of vitamin K epoxide reductase (VKOR). The challenge of VKAs therapy is their narrow therapeutic index and highly variable dosing requirements, which are partially the result of genetic variations of VKOR.<h4>Objectives</h4>The goal of this study was to search for an improved VKA that is tolerant to the genetic variations of its target enzyme.<h4>Methods</h4>A series of vitamin K derivatives with benzyl and related side-chain substitutions at the 3-position of 1,4-naphthoqJournal of thrombosis and haemostasis : JTHA novel vitamin K derived anticoagulant tolerant to genetic variations of vitamin K epoxide reductase.PMC7925372R01 HL131690FT110100851Liu YPaul Savage GWilliams CMJin DYChen XTie JKSuhara YFurukawa NStafford DWfalseA novel vitamin K derived anticoagulant tolerant to genetic variations of vitamin K epoxide reductase.<h4>Background</h4>Vitamin K antagonists (VKAs), such as warfarin, have remained the cornerstone of oral anticoagulation therapy in the prevention and treatment of thromboembolism for more than half a century. They function by impairing the biosynthesis of vitamin K-dependent (VKD) clotting factors through the inhibition of vitamin K epoxide reductase (VKOR). The challenge of VKAs therapy is their narrow therapeutic index and highly variable dosing requirements, which are partially the result of genetic variations of VKOR.<h4>Objectives</h4>The goal of this study was to search for an improved VKA that is tolerant to the genetic variations of its target enzyme.<h4>Methods</h4>A series of vitamin K derivatives with benzyl and related side-chain substitutions at the 3-position of 1,4-naphthoq2021-01-01T00:00:00Z2021 Mar2025-04-04T19:54:16.55Z2025-04-04T19:54:16.55ZS-EPMC79253723331462110.1111/jth.15209